Máster en Genética y Biología Celular OFERTA TRABAJO FIN DE MÁSTER-2015 Director: Ramón García Escudero, Científico Titular de la Unidad de Oncología Molecular del CIEMAT TITULO. Using next-generation sequencing (NGS) to discover long non-coding RNAs (lncRNAs) acting as oncogenes or tumor suppressors in cancers infected with human papillomavirus (HPV). PALABRAS CLAVE. Long non-coding RNA, lncRNA, RNAseq, precision medicine, next-generation sequencing, NGS, genomics, prognosis, diagnosis, cancer treatment, human papillomavirus, HPV, precision medicine. RESUMEN. Project will focus in computer analysis using RNAseq data from consortia such as The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) aiming to identify and validate new lncRNAs having association with biological, clinical and pathology features in HPV-infected oropharynx cancer and cervical cancer. Candidate lncRNAs would be targets for new antitumor therapies. Listado de las publicaciones incorporadas en la oferta. Kalathur M, Toso A, Chen J, Revandkar A, Danzer-Baltzer C, Guccini I, Alajati A, Sarti M, Pinton S, Brambilla L, Di Mitri D, Carbone G, Garcia-Escudero R, Padova A, Magnoni L, Tarditi A, Maccari L, Malusa F, Kalathur RK, A Pinna L, Cozza G, Ruzzene M, Delaleu N, Catapano CV, Frew IJ, Alimonti A. "A chemogenomic screening identifies CK2 as a target for pro-senescence therapy in PTEN-deficient tumours." Nat Commun 6: 7227-7227. (2015). (PMID: 26085373) Alajati A, Guccini I, Pinton S, Garcia-Escudero R, Bernasocchi T, Sarti M, Montani E, Rinaldi A, Montemurro F, Catapano C, Bertoni F, Alimonti A. "Interaction of CDCP1 with HER2 enhances HER2driven tumorigenesis and promotes trastuzumab resistance in breast cancer." Cell Rep 11(4): 564-576. (2015). (PMID: 25892239) Di Mitri D, Toso A, Chen JJ, Sarti M, Pinton S, Jost TR, D'Antuono R, Montani E, Garcia-Escudero R, Guccini I, Da Silva-Alvarez S, Collado M, Eisenberger M, Zheng Z, Catapano C, Grassi F, Alimonti A. "Tumour-infiltrating Gr-1(+) myeloid cells antagonize senescence in cancer." Nature : -. (2014). (PMID: 25156255) Toso A, Revandkar A, Di Mitri D, Guccini I, Proietti M, Sarti M, Pinton S, Zhang J, Kalathur M, Civenni G, Jarrossay D, Montani E, Marini C, Garcia-Escudero R, Scanziani E, Grassi F, Pandolfi PP, Catapano CV, Alimonti A. "Enhancing chemotherapy efficacy in Pten-deficient prostate tumors by activating the senescence-associated antitumor immunity." Cell Rep 9(1): 75-89. (2014). (PMID: 25263564) Civenni G, Malek A, Albino D, Garcia-Escudero R, Napoli S, Di Marco S, Pinton S, Sarti M, Carbone GM, Catapano CV. "RNAi-mediated silencing of Myc transcription inhibits stem-like cell maintenance and tumorigenicity in prostate cancer." Cancer Res 73(22): 6816-6827. (2013). (PMID: 24063893) Menacho-Márquez M, García-Escudero R, Ojeda V, Abad A, Delgado P, Costa C, Ruiz S, Alarcón B, Paramio JM, Bustelo XR. "The Rho exchange factors Vav2 and Vav3 favor skin tumor initiation and promotion by engaging extracellular signaling loops." PLoS Biol 11(7): e1001615-e1001615. (2013). (PMID: 23935450) Longoni N, Sarti M, Albino D, Civenni G, Malek A, Ortelli E, Pinton S, Mello-Grand M, Ostano P, D'Ambrosio G, Sessa F, Garcia-Escudero R, Thalmann GN, Chiorino G, Catapano CV, Carbone GM. "ETS transcription factor ESE1/ELF3 orchestrates a positive feedback loop that constitutively activates NF-κB and drives prostate cancer progression." Cancer Res 73(14): 4533-4547. (2013). (PMID: 23687337) Dueñas M, Santos M, Aranda JF, Bielza C, Martínez-Cruz AB, Lorz C, Taron M, Ciruelos EM, Rodríguez-Peralto JL, Martín M, Larrañaga P, Dahabreh J, Stathopoulos GP, Rosell R, Paramio JM, García-Escudero R. "Mouse p53-deficient cancer models as platforms for obtaining genomic predictors of human cancer clinical outcomes." PLoS ONE 7(8): e42494-e42494. (2012). (PMID: 22880004) García-Escudero R, Martínez-Cruz AB, Santos M, Lorz C, Segrelles C, Garaulet G, Saiz-Ladera C, Costa C, Buitrago-Pérez A, Dueñas M, Paramio JM. "Gene expression profiling of mouse p53-deficient epidermal carcinoma defines molecular determinants of human cancer malignancy." Mol. Cancer 9: 193193. (2010). (PMID: 20630075) Listado de publicaciones disponibles, no incorporadas en la oferta. Segrelles C, García-Escudero R, Garín MI, Aranda JF, Hernández P, Ariza JM, Santos M, Paramio JM, Lorz C. "Akt signaling leads to stem cell activation and promotes tumor development in epidermis." Stem Cells 32(7): 1917-1928. (2014). (PMID: 24504902) Santos M, Martínez-Fernández M, Dueñas M, García-Escudero R, Alfaya B, Villacampa F, Saiz-Ladera C, Costa C, Oteo M, Duarte J, Martínez V, Gómez-Rodriguez MJ, Martín ML, Fernández M, Viatour P, Morcillo MA, Sage J, Castellano D, Rodriguez-Peralto JL, de la Rosa F, Paramio JM. "In vivo disruption of an Rb-E2F-Ezh2 signaling loop causes bladder cancer." Cancer Res 74(22): 6565-6577. (2014). (PMID: 25252918) Costa C, Santos M, Martínez-Fernández M, Dueñas M, Lorz C, García-Escudero R, Paramio JM. "E2F1 loss induces spontaneous tumour development in Rb-deficient epidermis." Oncogene 32(24): 2937-2951. (2013). (PMID: 22890321) Dueñas M, Martínez-Fernández M, García-Escudero R, Villacampa F, Marqués M, Saiz-Ladera C, Duarte J, Martínez V, Gómez MJ, Martín ML, Fernández M, Castellano D, Real FX, Rodriguez-Peralto JL, De La Rosa F, Paramio JM. "PIK3CA gene alterations in bladder cancer are frequent and associate with reduced recurrence in non-muscle invasive tumors." Mol. Carcinog : -. (2013). (PMID: 24347284) Rivas V, Carmona R, Muñoz-Chápuli R, Mendiola M, Nogués L, Reglero C, Miguel-Martín M, GarcíaEscudero R, Dorn GW, Hardisson D, Mayor F, Penela P. "Developmental and tumoral vascularization is regulated by G protein-coupled receptor kinase 2." J. Clin. Invest 123(11): 4714-4730. (2013). (PMID: 24135140) Saiz-Ladera C, Lara MF, Garín M, Ruiz S, Santos M, Lorz C, García-Escudero R, Martínez-Fernández M, Bravo A, Fernández-Capetillo O, Segrelles C, Paramio JM. "p21 suppresses inflammation and tumorigenesis on pRB-deficient stratified epithelia." Oncogene : -. (2013). (PMID: 24121270) Chamorro C, Almarza D, Duarte B, Llames SG, Murillas R, García M, Cigudosa JC, Espinosa-Hevia L, Escámez MJ, Mencía A, Meana A, García-Escudero R, Moro R, Conti CJ, Del Río M, Larcher F. "Keratinocyte cell lines derived from severe generalized recessive epidermolysis bullosa patients carrying a highly recurrent COL7A1 homozygous mutation: models to assess cell and gene therapies in vitro and in vivo." Exp. Dermatol 22(9): 601-603. (2013). (PMID: 23947675) Quintana-Bustamante O, Grueso E, Garcia-Escudero R, Arza E, Alvarez-Barrientos A, Fabregat I, Garcia-Bravo M, Meza NW, Segovia JC. "Cell fusion reprogramming leads to a specific hepatic expression pattern during mouse bone marrow derived hepatocyte formation in vivo." PLoS ONE 7(3): e33945-e33945. (2012). (PMID: 22457803) Bornachea O, Santos M, Martínez-Cruz AB, García-Escudero R, Dueñas M, Costa C, Segrelles C, Lorz C, Buitrago A, Saiz-Ladera C, Agirre X, Grande T, Paradela B, Maraver A, Ariza JM, Prosper F, Serrano M, Sánchez-Céspedes M, Paramio JM. "EMT induction of miR-21 mediate metastasis development in Trp53-deficient tumours." Sci Rep 2: 434-434. (2012). (PMID: 22666537) Genini D, Garcia-Escudero R, Carbone GM, Catapano CV. "Transcriptional and Non-Transcriptional of PPARβ/δ in Non-Small Cell Lung Cancer." PLoS ONE 7(9): e46009-e46009. (2012). (PMID: 23049921) Citterio C, Menacho-Márquez M, García-Escudero R, Larive RM, Barreiro O, Sánchez-Madrid F, Paramio JM, Bustelo XR. "The rho exchange factors vav2 and vav3 control a lung metastasis-specific transcriptional program in breast cancer cells." Sci Signal 5(244): ra71-ra71. (2012). (PMID: 23033540) Buitrago-Pérez Á, Hachimi M, Dueñas M, Lloveras B, Santos A, Holguín A, Duarte B, Santiago JL, Akgül B, Rodríguez-Peralto JL, Storey A, Ribas C, Larcher F, del Rio M, Paramio JM, García-Escudero R. "A humanized mouse model of HPV-associated pathology driven by E7 expression." PLoS ONE 7(7): e41743-e41743. (2012). (PMID: 22911850) García-Hoz C, Sánchez-Fernández G, García-Escudero R, Fernández-Velasco M, Palacios-García J, Ruiz-Meana M, Díaz-Meco MT, Leitges M, Moscat J, García-Dorado D, Boscá L, Mayor F, Ribas C. "Protein kinase C (PKC)ζ-mediated Gαq stimulation of ERK5 protein pathway in cardiomyocytes and cardiac fibroblasts." J. Biol. Chem 287(10): 7792-7802. (2012). (PMID: 22232556) Pippa R, Espinosa L, Gundem G, García-Escudero R, Dominguez A, Orlando S, Gallastegui E, Saiz C, Besson A, Pujol MJ, López-Bigas N, Paramio JM, Bigas A, Bachs O. "p27Kip1 represses transcription by direct interaction with p130/E2F4 at the promoters of target genes." Oncogene 31(38): 4207-4220. (2012). (PMID: 22179826) Akgül B, García-Escudero R, Ekechi C, Steger G, Navsaria H, Pfister H, Storey A. "The E2 protein of human papillomavirus type 8 increases the expression of matrix metalloproteinase-9 in human keratinocytes and organotypic skin cultures." Med. Microbiol. Immunol 200(2): 127-135. (2011). (PMID: 21274725) Lorz C, García-Escudero R, Segrelles C, Garín MI, Ariza JM, Santos M, Ruiz S, Lara MF, Martínez-Cruz AB, Costa C, Buitrago-Pérez A, Saiz-Ladera C, Dueñas M, Paramio JM. "A functional role of RBdependent pathway in the control of quiescence in adult epidermal stem cells revealed by genomic profiling." Stem Cell Rev 6(2): 162-177. (2010). (PMID: 20376578) García-Escudero R, Paramio JM. "Gene expression profiling of mouse epidermal keratinocytes." Methods Mol. Biol 585: 171-181. (2010). (PMID: 19908004) Moral M, Segrelles C, Martínez-Cruz AB, Lorz C, Santos M, García-Escudero R, Lu J, Buitrago A, Costa C, Saiz C, Ariza JM, Dueñas M, Rodriguez-Peralto JL, Martinez-Tello FJ, Rodriguez-Pinilla M, SanchezCespedes M, Digiovanni J, Paramio JM. "Transgenic mice expressing constitutively active Akt in oral epithelium validate KLFA as a potential biomarker of head and neck squamous cell carcinoma." In Vivo 23(5): 653-660. (2009). (PMID: 19779097) Martínez-Cruz AB, Santos M, García-Escudero R, Moral M, Segrelles C, Lorz C, Saiz C, Buitrago-Pérez A, Costa C, Paramio JM. "Spontaneous tumor formation in Trp53-deficient epidermis mediated by chromosomal instability and inflammation." Anticancer Res 29(8): 3035-3042. (2009). (PMID: 19661312) Moral M, Segrelles C, Lara MF, Martínez-Cruz AB, Lorz C, Santos M, García-Escudero R, Lu J, Kiguchi K, Buitrago A, Costa C, Saiz C, Rodriguez-Peralto JL, Martinez-Tello FJ, Rodriguez-Pinilla M, SanchezCespedes M, Garín M, Grande T, Bravo A, DiGiovanni J, Paramio JM. "Akt activation synergizes with Trp53 loss in oral epithelium to produce a novel mouse model for head and neck squamous cell carcinoma." Cancer Res 69(3): 1099-1108. (2009). (PMID: 19176372) Buitrago-Pérez A, Garaulet G, Vázquez-Carballo A, Paramio JM, García-Escudero R. "Molecular Signature of HPV-Induced Carcinogenesis: pRb, p53 and Gene Expression Profiling." Curr. Genomics 10(1): 26-34. (2009). (PMID: 19721808) Lara MF, Santos M, Ruiz S, Segrelles C, Moral M, Martínez-Cruz AB, Hernández P, Martínez-Palacio J, Lorz C, García-Escudero R, Paramio JM. "p107 acts as a tumor suppressor in pRb-deficient epidermis." Mol. Carcinog 47(2): 105-113. (2008). (PMID: 17932945) Lara MF, García-Escudero R, Ruiz S, Santos M, Moral M, Martínez-Cruz AB, Segrelles C, Lorz C, Paramio JM. "Gene profiling approaches help to define the specific functions of retinoblastoma family in epidermis." Mol. Carcinog 47(3): 209-221. (2008). (PMID: 17932948) Segrelles C, Moral M, Lorz C, Santos M, Lu J, Cascallana JL, Lara MF, Carbajal S, Martínez-Cruz AB, García-Escudero R, Beltran L, Segovia JC, Bravo A, DiGiovanni J, Paramio JM. "Constitutively active Akt induces ectodermal defects and impaired bone morphogenetic protein signaling." Mol. Biol. Cell 19(1): 137-149. (2008). (PMID: 17959825) Martínez-Cruz AB, Santos M, Lara MF, Segrelles C, Ruiz S, Moral M, Lorz C, García-Escudero R, Paramio JM. "Spontaneous squamous cell carcinoma induced by the somatic inactivation of retinoblastoma and Trp53 tumor suppressors." Cancer Res 68(3): 683-692. (2008). (PMID: 18245467) Santos M, Ruiz S, Lara MF, Segrelles C, Moral M, Martínez-Cruz AB, Ballestín C, Lorz C, GarcíaEscudero R, Paramio JM. "Susceptibility of pRb-deficient epidermis to chemical skin carcinogenesis is dependent on the p107 allele dosage." Mol. Carcinog 47(11): 815-821. (2008). (PMID: 18300254) García-Escudero R, Paramio JM. "Gene expression profiling as a tool for basic analysis and clinical application of human cancer." Mol. Carcinog 47(8): 573-579. (2008). (PMID: 18324660) Segrelles C, Lu J, Hammann B, Santos M, Moral M, Cascallana JL, Lara MF, Rho O, Carbajal S, Traag J, Beltrán L, Martínez-Cruz AB, García-Escudero R, Lorz C, Ruiz S, Bravo A, Paramio JM, DiGiovanni J. "Deregulated activity of Akt in epithelial basal cells induces spontaneous tumors and heightened sensitivity to skin carcinogenesis." Cancer Res 67(22): 10879-10888. (2007). (PMID: 18006833) Leverrier S, Bergamaschi D, Ghali L, Ola A, Warnes G, Akgül B, Blight K, García-Escudero R, Penna A, Eddaoudi A, Storey A. "Role of HPV E6 proteins in preventing UVB-induced release of pro-apoptotic factors from the mitochondria." Apoptosis 12(3): 549-560. (2007). (PMID: 17195958) Redrejo-Rodríguez M, García-Escudero R, Yáñez-Muñoz RJ, Salas ML, Salas J. "African swine fever virus protein pE296R is a DNA repair apurinic/apyrimidinic endonuclease required for virus growth in swine macrophages." J. Virol 80(10): 4847-4857. (2006). (PMID: 16641276) Segrelles C, Moral M, Lara MF, Ruiz S, Santos M, Leis H, García-Escudero R, Martínez-Cruz AB, Martínez-Palacio J, Hernández P, Ballestín C, Paramio JM. "Molecular determinants of Akt-induced keratinocyte transformation." Oncogene 25(8): 1174-1185. (2006). (PMID: 16247457) Akgül B, García-Escudero R, Ghali L, Pfister HJ, Fuchs PG, Navsaria H, Storey A. "The E7 protein of cutaneous human papillomavirus type 8 causes invasion of human keratinocytes into the dermis in organotypic cultures of skin." Cancer Res 65(6): 2216-2223. (2005). (PMID: 15781634) Akgül B, Lemme W, García-Escudero R, Storey A, Pfister HJ. "UV-B irradiation stimulates the promoter activity of the high-risk, cutaneous human papillomavirus 5 and 8 in primary keratinocytes." Arch. Virol 150(1): 145-151. (2005). (PMID: 15654507) Giampieri S, García-Escudero R, Green J, Storey A. "Human papillomavirus type 77 E6 protein selectively inhibits p53-dependent transcription of proapoptotic genes following UV-B irradiation." Oncogene 23(34): 5864-5870. (2004). (PMID: 15077176)
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